The manner in which human immunoglobulins and cellular products are able to activate the properdin system will be studied. Specifically, different classes and subclasses of myeloma proteins, antibodies and cellular products such as (lysosomal) enzymes and membrane constituents will be analyzed for their capacity to activate this system. The points at which these substances act in the reaction sequence of the properdin system will be determined and the activating capacity of different immunoglobulin fragments will be compared. Plasma and serum fractions and the known proteinase inhibitors of human plasma will be checked for their ability to inhibit the properdin system and their mode of inter-action with components of the system will be determined. Experiments will be conducted to determine the sites of biosynthesis of the properdin system proteins, properdin, C3, C3 proactivator (C3PA), C3 proactivator convertase (C3PAse), C3b inactivator (C3bINA) and other factors or inhibitors which may be identified in the future. Various normal and malignant human and animal tissues and blood cells as well as established continuous cell lines will be analyzed in tissue culture systems for their capacity to synthesize these components. Internal labeling through incorporation of radiolabeled amino acids and the use of specific antisera will aid in the detection and quantitation of these proteins in the tissue culture medium. In addition, functional assays for single components will be used. The absence or presence of properdin, C3, C3PA, C3PAse and C3bINA on or inside cells will be ascertained by the use of fluorescently labeled antisera.